- Can also be viral (HSV, EBV, adenovirus) etc 

⭐

• Chlamydia is extremely common (1/10 young women in the UK)
• Obligate intracellular, gram -ve Bacteria.
  • If symptomatic, commonest symptoms are dysuria, dyspereunia, vaginal discharge, intermenstrual spotting.
• Testing should be done 2 weeks after exposure.
• red staining ⭐inclusion bodies are seen in infected cells.
• Complications: epididymitis, perihepatitis, ⬆ectopic risk, endometritis, infertility.
• Management ⭐Doxycycline; azithro is no longer preferred due to high rate of coninfection with mycoplasma genitalium (which is resistant to azithro)
  • If pregnant then azithromycin
• Contact screening is done.

Mnemonic: Can't Have Good Sex on a Tricycle

• Trichomonas is a motile protozoan

[!TIP] Mnemonic: Gardner's don't harm the garden -> G.vaginalis doesn't cause inflammation
Therefore, clear discharge. (but fishy smell)

⭐

• Clear discharge, non itchy
• Overgrowth of gardnerella causes decrease in lactobacilli, which increases vaginal pH.

3. Friedrich's ataxia (but this does not show anticipation since it is an #autosomal-Recessive disease and disease is usually not seen in > 1 generation) Source

CMV infection (cytomegalovirus)

A family history in which males and females are affected, affected females transmit the disease to ⭐ALL their children, and affected males do not transmit the disease to their children suggests mitochondrial inheritance
Mitochondria produce energy. Mitochondrial disease are diseases which arise because of defects in the respiratory chain as 13 respiratory proteins are encoded by mitrochondrial DNA.

• sensorineural deafness, optic atrophy, pigmentary retinopathy, and
  Heteroplasmy - the fact that genome varies between mitochondria in a single cell. So.. only some daughter oocytes may get the bad mitochondria. -> therefore, disease phenotype is variable among siblings.

Refsum disease - previousyl hereditary sensory motor neuropathy IV.

• Four classic features:
  1. Retinitis pigmentosa
  2. Polyneuropathy - numbness, tinglig or loss of reflexes
  3. Cerebellar ataxia
  4. CSF cytoprotein dissociation (which high protein but no pleocytosis)
• #autosomal-Recessive , Classic refsum -> excessive phytanic acid accumulation. (basis is a disorder of peroxisomal function)
  • ⬆ phytanic acid is used for diagnosis.

⭐

Tay Sach's disease

Pathology of cancers

• Reprogramming of stem cells to differentiate into a cell type that is more suitable to cope with the new stresses than the original cell type at that location. Can occur in epithleal OR mesenchyal cells.
• I.e results in replacement of one type of mature cell with another type of mature cell.
• It is a reversible change;
• Example: Squamous metaplasia of respiratory epithelium in smokers.
• Vitamin A is essential for normal epithelial differentiation.

⭐Dysplasia:

• "Anarchy or normal cellular order" ->
• However, mild to moderate dysplasia can spotaneously regress as well.

Chronic granulomatous disease

• Is a cause for staphylococcal infections.
• The defects are either #x-linked-recessive recessive or #autosomal-Recessive.
• Impaired production of free radicals which needed to kill bacteria.
• I.e Phagocytosis is intact but killing is impaired.
• Presentation: Recurring infections (due to catalase producing organisms like staph aureus, E. coli, klebsiella etc) since childhood or early adolescence with systemic granuloma formation (lungs, liver, lymph nodes etc).
• Treatment: Prophylactic antibiotics (TMP-SMX) and in severe infection, granulocyte transfusion. Interferron gamma is also used for treatment.

Anaplastic CA grows rapidly. Many patients present with local invasion (unresectable tumours) or cervial lymph node metastasis.

• They will present with stridor or hoarseness.
• On histology, the tumour retains features of epithelial cells (presence of desmosomes) but there are large areas of necrosis and bleeding. There is high mitotic activity.

Vessel injury of any cause produces the same stereotyped response. Intimal thickening is a stereotypical response to vessel injury.
Mechanism: Intimal injury stimulates migration of smooth muscle cells from the media OR from circulating precursors!. They arrive in the intima, undergo mitosis and produces extracellular matrix, forming a 'neointima'. This is analogous to scar formation elsewhere. Neointimal smooth muscle cells are non contractile but can undergo mitosis and have greater synthetic capacity. This altered activation of neointimal smooth muscle cells is driven by cytokines produced by platelets, macrophages, endothelial cells and circulating complement and coagulation factors. Cytokines involved are PDGF, FGF, TGF-alpha (Platelet derived growth factors, Fibroblast growth factors, TGF-alpha).

• High intake of saturated fats raises lipid levels.
• Trans unsaturated fats found in margarine are bad.
• Exercise and moderate consumption of ⭐ethanol raises HDL levels.
• CRP produced by 'cells in the plaque' increase adhesiveness of endothelial cells and CRP independently and strongly correlated with risk of infarction.
• Lipoprotein a increases risk.
• Neovascularization produces vessels which can rupture into the plaque and cause haemorrhage into it.
  1. Any condition increases blood lipid levels. (LDL, IDL etc)
     In the presence of lipids within the intima, macrophages become activated. When they engulf lipids, they become foam cells.
     Smooth muscle cells proliferate and take on fibroblastic roles.
• Smooth muscles + collagen produced by them form the fibrous cap of the plaque.

  1. **Endothelial dysfunction** is promoted mainly by altered haemodynamics and hypercholesterolemia.
  2. **Dysfunctional endothelium** promotes adhesion of inflmmatory cells including macrophages (which *engulf LDL* to become foam cells)  and T lymphocytes (which set up chronic inflammation). 

• The earliest lesion is a Fatty streak. Composed of Foam cells but not raised.
• ⭐Aortic fatty streaks are present in all children.
• ⭐Coronary fatty streaks form during adolescence.
  - Upper limbs, renal arteries and mesenteric arteries are usually spared.
  - Lesions at various stages coexist in the same vessel.

The majority of plaque ruptures occurs in the proximal and middle of coronary arteries and distal ruptures are rare.

Immunoglobulin / antibody classes

The primary humoral immune response to a novel pathogen typically requires close to a week before substantial amounts of IgM appear in the blood, and the innate immune response is necessary to fight the infection until the creation of T cells and antibody-secreting plasma cells clonally expanded against the pathogen in sufficient numbers. Source

Neutrophil defects

> Is with recurrent and severe bacterial (Staphylococcus, pseudomonas, salmonella, Nocardia) and fungal (candida, Aspergillus) infections, most commonly of the respiratory tract and skin.

Inherited neutorphil defects

1. [[2022 May Basic Sciences#Chronic granulomatous disease|Chronic Granulomatous disease]] <- a defect in neutrophil killing. (defect in ROS production)
   • Presents in early life with ⭐delayed umbilical cord separation, failure to lose primary dentition, severe gingivitis. There is ⭐neutrophilia but the cells cannot reach sites of infection. Recurrent infections in the first decade of life. Treatment is stem cell transplant.
2. Hyper IgE syndrome - Job's syndrome
   • ⭐ #autosomalDominant
   • abnormal T cell function, increased IgE production and ⭐intermittent defects in neutrophil chemotaxis.
   • Dermatitis, boils, pneumonia
3. Schwachman-Diamond syndrome ^226faf
4. Chediak-Higashi syndrome
   • One cause of primary haemophagocytic lymphohistiocytosis [[Anaemia#Haemophagocytic lymphohistiocytosis]].

Acquired neutrophil defects / neutropenia

• Chronic dialysis : Adhesion and chemotaxis defects.

Therefore,⭐ POEMS is a paraproteinaemic neuropathy.
P - ⭐demyelinating polyneuropathy.

A) Hyperpigmentation. (B) Hypertrichosis. (C) A typical hemangioma. (D) Hemangiomas with darkened mammary areola. (E) White nails. (F) Acrocyanosis. (G) Dry skin and ichthyosis-like lesions
Source